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  • 1
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Lokalanästhetika: Bupivacain ; Toxizität: Lokalanästhetika ; Key words Anaesthetics ; local ; Bupivacaine ; Cerebroventricular perfusion ; Toxicity: local anaesthetics ; CNS effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Objectives: The cardiotoxic properties of bupivacain have been well documented under in-vitro, as well as under in-vivio conditions. A further mechanism of cardiovascular impairment by bupivacaine via the central nervous system gained investigational interest in animal studies. The aim of our study was to demonstrate the effect of a ventriculocisternal perfusion of bupivacain on systemic hemodynamic variabels and their reversability by wash-out with mock-CSF. Methods: After obtaining animal investional commitee consent, nine anaesthetized and relaxated pigs were prepared for a ventriculocisternal perfusion (VCP). Hemodynamic data were obtained by invasive blood pressure measurements in the high and low pressure system as well as cardiac output (thermodilution technique), intracranial pressure and electrocardiogram. Systemic vascular resistance and stroke volume were calculated using standard formulas. A second group of three animals were exposed to an intravenous infusion of the same dose of bupivacain over the same period of time to rule out direct cardiac effects. After instrumentation baseline data were obtained (KO 1) under VCP with mock-CSF for 30 minutes. The mock-CSF was replaced by 0,05% bupivacaine in mock-CSF and VCP was continued with 3 ml · h–1 for 20 minutes. After adminstration of 500 µg bupivacaine data were collected (BU). The bupivacaine solution was replaced by mock-CSF and after twenty minutes hemodynamic measurement were repeated (KO2). Results: The intravenous adminstration of 500µg bupivacaine had no effect on all measured variables. VCP of the same dose resulted in significant increase in heart rate, systolic, diastolic and mean arterial blood pressures. Left and right heart filling pressures as well as systemic vascular resistance were not affected while the stroke volume decreased. After continuation of VCP with mock-CSF hemodynamic changes were reversed. Discussion: Our results demonstrate that bupivacaine initiates an indirect cardiovascular stimulating effect of a VCP with 500 µg of bupivacaine via the central nervous system. The intravenous administration of the same dose had no effect. The centrally mediated cardiovascular effect of bupivacaine was reversed by wash-out with mock-CSF. The cardiovascular stimulation observed in this animal experiment may be of clinical relevance as a potential sign of toxic effects of bupivacaine on the CNS.
    Notes: Zusammenfassung Die in vitro nachweisbaren kardiotoxischen Eigenschaften des Bupivacains sind weitgehend bekannt, eine weitere, über das Zentralnervensystem vermittelte Beeinflussung des Herzkreislaufsystems wird dagegen diskutiert. Ziel dieser Studie war es, die Auswirkungen der zentral vemittelten Bupivacainwirkung auf systemische Kreislaufparameter und deren Reversibilität durch Auswaschung mit künstlichem Liquor (m-CSF) tierexperimentell zu untersuchen. Methodik: Dazu wurden nach Genehmigung durch die Tierschutzkommission 9 anästhesierte Jungschweine für eine ventrikulozisternale Perfusion (VCP) mit insgesamt 500 µg Bupivacain in m-CSF präpariert. Die Messungen umfaßten neben invasiv registrierten Blutdrücken im kleinen und großen Kreislauf Herzzeitvolumen, intrakraniellen Druck und Elektrokardiogramm. Der periphere Widerstand und das Schlagvolumen wurden berechnet. Zusätzlich wurde drei Tieren einer Kontrollgruppe Bupivacain 500 µg zum Ausschluß einer direkt kardialen Wirkung intravenös appliziert. Nach einer Stabilisierungsphase im Anschluß an die Präparation wurden Ausgangswerte unter einer VCP mit m-CSF erhoben (KO 1). Danach wurde die VCP über 20 min mit Bupivacain in m-CSF fortgeführt und eine weitere Messung angeschlossen (BU). Die dritte Messung erfolgte nach VCP nur mit m-CSF über 20 min (KO 2). Ergebnisse: Die ventrikulo-zisternale Perfusion von 500 µg Bupivacain führte zu einem Anstieg des systolischen, diastolischen und mittleren arteriellen Bludrucks, der Herzfrequenz und des Herzzeitvolumens. Die rechts- und linksventrikulären Füllungsdrücke sowie der periphere Widerstand blieben unbeeinflußt. Das Schlagvolumen nahm signifikant ab. Mit der Auswaschung (KO 2) waren alle Kreislaufeffekte vollständig reversibel. Bei der intravenösen Infusion der gleichen Bupivacainmenge traten keine Änderungen in den gemessenen Variablen auf. Schlußfolgerungen: Nach unseren Ergebnissen führte die VCP mit 500 µg Bupivacain im Gegensatz zur intravenösen Infusion zu einer signifikanten, zentral vermittelten Kreislaufstimulation, die unter Fortführung der VCP mit m-CSF durch eine Verdünnung oder Auswaschung innerhalb von 20 min vollständig reversibel ist. Den beobachteten Kreislaufeffekten könnte für die frühzeitige Erkennung einer unerwünschten Reaktion auf Bupivacain für die klinische Routine Bedeutung zukommen.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neuroimmune interactions are discussed to drive neuropathic pain. We used the Bennett model to correlate pain and cellular expression profiles of the complement factors C1q and C1q-associated serine proteases C1r/C1s in lumbar spinal cord. At 2 days C1q mRNA levels increased ipsilateral to the lesion, and peaked at 8 days when allodynia and severe walking problems were present. During regeneration walking problems disappeared together with C1q mRNA levels. C1q biosynthesis was restricted to microglia. Surprisingly, C1s/C1r biosynthesis was not increased after injury suggesting a role for C1q different from classical complement activation. Sustained C1q expression in spinal microglia after lesion in conjunction with pain behavior indicates that microglial C1q may be causally involved in the development and maintenance of neuropathic pain.Acknowledgements:  Supported by BMBF01GG9818, SFB297, DFGWE910/8-3, KBN3P05C00623.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Peptides participating in the hypothalamic control of feeding behaviour are also involved in the central autonomic control of gastrointestinal functions, such as secretion and motility. An anatomical interaction and functional relationship in the central nervous system between the feeding-related peptides neuropeptide Y and ghrelin is well documented. Furthermore, it has been shown that feeding-related peptides can influence digestive function via central corticotrophin-releasing factor (CRF) pathways. In the present study, we investigated the role of ghrelin in the central autonomic control of colonic motility. Furthermore, we addressed the hypothesis that ghrelin is involved in the hypothalamic control of colonic motor function, utilizing central neuropeptide Y receptors and hypothalamic CRF pathways. Ghrelin (0.03, 0.06 and 0.12 nmol) bilaterally microinjected into the paraventricular nucleus (PVN) induced a significant stimulation of colonic propulsion. In particular, the colonic transit time decreased from 312 ± 7 min to 198 ± 12 min. Microinjection of the neuropeptide Y1 receptor antagonist, BIBP-3226 (200 pmol), or the nonselective CRF receptor antagonist, astressin (30 pmol), into the PVN abolished the stimulatory effect of ghrelin injected into the PVN on colonic transit time, whereas pretreatment with the selective CRF2 receptor, antisauvagine-30 (28 pmol), failed to affect the effect of PVN-ghrelin injection on colonic propulsion. These results suggest that ghrelin can act as central modulator of gastrointestinal motor functions at the level of the PVN via neuropeptide Y1- and CRF1 receptor-dependent mechanisms.
    Type of Medium: Electronic Resource
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